WO2021170138A1 - 抗肿瘤组合物 - Google Patents
抗肿瘤组合物 Download PDFInfo
- Publication number
- WO2021170138A1 WO2021170138A1 PCT/CN2021/078437 CN2021078437W WO2021170138A1 WO 2021170138 A1 WO2021170138 A1 WO 2021170138A1 CN 2021078437 W CN2021078437 W CN 2021078437W WO 2021170138 A1 WO2021170138 A1 WO 2021170138A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cancer
- tumor
- bifidobacterium longum
- mice
- immune checkpoint
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 25
- 230000000259 anti-tumor effect Effects 0.000 title claims abstract description 20
- 241001608472 Bifidobacterium longum Species 0.000 claims abstract description 76
- 229940009291 bifidobacterium longum Drugs 0.000 claims abstract description 75
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 67
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 claims abstract description 30
- 102000037984 Inhibitory immune checkpoint proteins Human genes 0.000 claims abstract description 30
- 108091008026 Inhibitory immune checkpoint proteins Proteins 0.000 claims abstract description 30
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 claims abstract description 30
- 229940079593 drug Drugs 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims abstract description 5
- 238000002347 injection Methods 0.000 claims description 20
- 239000007924 injection Substances 0.000 claims description 20
- 230000000694 effects Effects 0.000 claims description 18
- 206010006187 Breast cancer Diseases 0.000 claims description 15
- 208000026310 Breast neoplasm Diseases 0.000 claims description 15
- 239000003242 anti bacterial agent Substances 0.000 claims description 13
- 229940088710 antibiotic agent Drugs 0.000 claims description 13
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 11
- 201000005202 lung cancer Diseases 0.000 claims description 11
- 208000020816 lung neoplasm Diseases 0.000 claims description 11
- 201000001441 melanoma Diseases 0.000 claims description 9
- 241000186000 Bifidobacterium Species 0.000 claims description 8
- 206010009944 Colon cancer Diseases 0.000 claims description 8
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 8
- 206010038389 Renal cancer Diseases 0.000 claims description 8
- 208000029742 colonic neoplasm Diseases 0.000 claims description 8
- 201000010982 kidney cancer Diseases 0.000 claims description 8
- 206010044412 transitional cell carcinoma Diseases 0.000 claims description 8
- 241000894006 Bacteria Species 0.000 claims description 4
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 4
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 4
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 4
- 201000010881 cervical cancer Diseases 0.000 claims description 4
- 206010017758 gastric cancer Diseases 0.000 claims description 4
- 201000010536 head and neck cancer Diseases 0.000 claims description 4
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 4
- 201000007270 liver cancer Diseases 0.000 claims description 4
- 208000014018 liver neoplasm Diseases 0.000 claims description 4
- 201000011549 stomach cancer Diseases 0.000 claims description 4
- 241000193403 Clostridium Species 0.000 claims description 3
- 241000194031 Enterococcus faecium Species 0.000 claims description 3
- 241000186660 Lactobacillus Species 0.000 claims description 3
- 206010025323 Lymphomas Diseases 0.000 claims description 3
- 241000605861 Prevotella Species 0.000 claims description 3
- 229940039696 lactobacillus Drugs 0.000 claims description 3
- 210000004767 rumen Anatomy 0.000 claims 1
- 239000012270 PD-1 inhibitor Substances 0.000 abstract description 6
- 239000012668 PD-1-inhibitor Substances 0.000 abstract description 6
- 229940121655 pd-1 inhibitor Drugs 0.000 abstract description 6
- 229940045513 CTLA4 antagonist Drugs 0.000 abstract description 5
- 239000012275 CTLA-4 inhibitor Substances 0.000 abstract description 4
- 239000012271 PD-L1 inhibitor Substances 0.000 abstract description 2
- 229940121656 pd-l1 inhibitor Drugs 0.000 abstract description 2
- 241000699670 Mus sp. Species 0.000 description 39
- 210000004881 tumor cell Anatomy 0.000 description 34
- 230000003115 biocidal effect Effects 0.000 description 28
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 24
- 238000011081 inoculation Methods 0.000 description 19
- 210000004027 cell Anatomy 0.000 description 18
- 229940090044 injection Drugs 0.000 description 13
- 241000699666 Mus <mouse, genus> Species 0.000 description 12
- 229960005322 streptomycin Drugs 0.000 description 12
- 230000004614 tumor growth Effects 0.000 description 11
- 229960000723 ampicillin Drugs 0.000 description 7
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 7
- 238000013227 male C57BL/6J mice Methods 0.000 description 7
- 108010078777 Colistin Proteins 0.000 description 6
- 229930182555 Penicillin Natural products 0.000 description 6
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 6
- 238000010171 animal model Methods 0.000 description 6
- -1 benzoxacillin Chemical compound 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 6
- 230000000968 intestinal effect Effects 0.000 description 6
- 229940049954 penicillin Drugs 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- 230000003698 anagen phase Effects 0.000 description 5
- 239000000427 antigen Substances 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 229960003346 colistin Drugs 0.000 description 5
- 239000012091 fetal bovine serum Substances 0.000 description 5
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 5
- 210000002865 immune cell Anatomy 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- JORAUNFTUVJTNG-BSTBCYLQSA-N n-[(2s)-4-amino-1-[[(2s,3r)-1-[[(2s)-4-amino-1-oxo-1-[[(3s,6s,9s,12s,15r,18s,21s)-6,9,18-tris(2-aminoethyl)-3-[(1r)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-h Chemical compound CC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O.CCC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O JORAUNFTUVJTNG-BSTBCYLQSA-N 0.000 description 5
- XDJYMJULXQKGMM-UHFFFAOYSA-N polymyxin E1 Natural products CCC(C)CCCCC(=O)NC(CCN)C(=O)NC(C(C)O)C(=O)NC(CCN)C(=O)NC1CCNC(=O)C(C(C)O)NC(=O)C(CCN)NC(=O)C(CCN)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCN)NC1=O XDJYMJULXQKGMM-UHFFFAOYSA-N 0.000 description 5
- KNIWPHSUTGNZST-UHFFFAOYSA-N polymyxin E2 Natural products CC(C)CCCCC(=O)NC(CCN)C(=O)NC(C(C)O)C(=O)NC(CCN)C(=O)NC1CCNC(=O)C(C(C)O)NC(=O)C(CCN)NC(=O)C(CCN)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCN)NC1=O KNIWPHSUTGNZST-UHFFFAOYSA-N 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 241000282414 Homo sapiens Species 0.000 description 4
- 101000894590 Homo sapiens Uncharacterized protein C20orf85 Proteins 0.000 description 4
- 102000037982 Immune checkpoint proteins Human genes 0.000 description 4
- 108091008036 Immune checkpoint proteins Proteins 0.000 description 4
- 102100021442 Uncharacterized protein C20orf85 Human genes 0.000 description 4
- 230000006978 adaptation Effects 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 239000003651 drinking water Substances 0.000 description 4
- 235000020188 drinking water Nutrition 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 3
- 102100022338 Integrin alpha-M Human genes 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000003304 gavage Methods 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000003223 protective agent Substances 0.000 description 3
- 102100028990 C-X-C chemokine receptor type 3 Human genes 0.000 description 2
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 2
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 2
- 101150013553 CD40 gene Proteins 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- 102100027581 Forkhead box protein P3 Human genes 0.000 description 2
- 102000001398 Granzyme Human genes 0.000 description 2
- 108060005986 Granzyme Proteins 0.000 description 2
- 101000916050 Homo sapiens C-X-C chemokine receptor type 3 Proteins 0.000 description 2
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 2
- 101000861452 Homo sapiens Forkhead box protein P3 Proteins 0.000 description 2
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 2
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 2
- 101000916644 Homo sapiens Macrophage colony-stimulating factor 1 receptor Proteins 0.000 description 2
- 101000576894 Homo sapiens Macrophage mannose receptor 1 Proteins 0.000 description 2
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 2
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 2
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 2
- 102100028198 Macrophage colony-stimulating factor 1 receptor Human genes 0.000 description 2
- 102100025354 Macrophage mannose receptor 1 Human genes 0.000 description 2
- 101100013967 Mus musculus Gata3 gene Proteins 0.000 description 2
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 2
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 2
- WKDDRNSBRWANNC-UHFFFAOYSA-N Thienamycin Natural products C1C(SCCN)=C(C(O)=O)N2C(=O)C(C(O)C)C21 WKDDRNSBRWANNC-UHFFFAOYSA-N 0.000 description 2
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- 239000002647 aminoglycoside antibiotic agent Substances 0.000 description 2
- 229950002916 avelumab Drugs 0.000 description 2
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 238000002619 cancer immunotherapy Methods 0.000 description 2
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002550 fecal effect Effects 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 229960002182 imipenem Drugs 0.000 description 2
- ZSKVGTPCRGIANV-ZXFLCMHBSA-N imipenem Chemical compound C1C(SCC\N=C\N)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 ZSKVGTPCRGIANV-ZXFLCMHBSA-N 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000003120 macrolide antibiotic agent Substances 0.000 description 2
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000002132 β-lactam antibiotic Substances 0.000 description 2
- 229940124586 β-lactam antibiotics Drugs 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- RXZBMPWDPOLZGW-XMRMVWPWSA-N (E)-roxithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=N/OCOCCOC)/[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 RXZBMPWDPOLZGW-XMRMVWPWSA-N 0.000 description 1
- 229930183010 Amphotericin Natural products 0.000 description 1
- QGGFZZLFKABGNL-UHFFFAOYSA-N Amphotericin A Natural products OC1C(N)C(O)C(C)OC1OC1C=CC=CC=CC=CCCC=CC=CC(C)C(O)C(C)C(C)OC(=O)CC(O)CC(O)CCC(O)C(O)CC(O)CC(O)(CC(O)C2C(O)=O)OC2C1 QGGFZZLFKABGNL-UHFFFAOYSA-N 0.000 description 1
- WZPBZJONDBGPKJ-UHFFFAOYSA-N Antibiotic SQ 26917 Natural products O=C1N(S(O)(=O)=O)C(C)C1NC(=O)C(=NOC(C)(C)C(O)=O)C1=CSC(N)=N1 WZPBZJONDBGPKJ-UHFFFAOYSA-N 0.000 description 1
- 241000606124 Bacteroides fragilis Species 0.000 description 1
- JMGZEFIQIZZSBH-UHFFFAOYSA-N Bioquercetin Natural products CC1OC(OCC(O)C2OC(OC3=C(Oc4cc(O)cc(O)c4C3=O)c5ccc(O)c(O)c5)C(O)C2O)C(O)C(O)C1O JMGZEFIQIZZSBH-UHFFFAOYSA-N 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 102100025248 C-X-C motif chemokine 10 Human genes 0.000 description 1
- 101710098275 C-X-C motif chemokine 10 Proteins 0.000 description 1
- 102100036170 C-X-C motif chemokine 9 Human genes 0.000 description 1
- 101710085500 C-X-C motif chemokine 9 Proteins 0.000 description 1
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- IIUZTXTZRGLYTI-UHFFFAOYSA-N Dihydrogriseofulvin Natural products COC1CC(=O)CC(C)C11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 IIUZTXTZRGLYTI-UHFFFAOYSA-N 0.000 description 1
- UIOFUWFRIANQPC-JKIFEVAISA-N Floxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=C(F)C=CC=C1Cl UIOFUWFRIANQPC-JKIFEVAISA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- UXWOXTQWVMFRSE-UHFFFAOYSA-N Griseoviridin Natural products O=C1OC(C)CC=C(C(NCC=CC=CC(O)CC(O)C2)=O)SCC1NC(=O)C1=COC2=N1 UXWOXTQWVMFRSE-UHFFFAOYSA-N 0.000 description 1
- 206010018852 Haematoma Diseases 0.000 description 1
- 101000935040 Homo sapiens Integrin beta-2 Proteins 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- IEMDOFXTVAPVLX-YWQHLDGFSA-N Leucomycin A1 Chemical compound CO[C@H]1[C@H](O)CC(=O)O[C@H](C)C\C=C\C=C\[C@H](O)[C@H](C)C[C@H](CC=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](N(C)C)[C@H](O[C@@H]2O[C@@H](C)[C@H](OC(=O)CC(C)C)[C@](C)(O)C2)[C@@H](C)O1 IEMDOFXTVAPVLX-YWQHLDGFSA-N 0.000 description 1
- GSDSWSVVBLHKDQ-JTQLQIEISA-N Levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 description 1
- OJMMVQQUTAEWLP-UHFFFAOYSA-N Lincomycin Natural products CN1CC(CCC)CC1C(=O)NC(C(C)O)C1C(O)C(O)C(O)C(SC)O1 OJMMVQQUTAEWLP-UHFFFAOYSA-N 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 1
- 101000962498 Macropis fulvipes Macropin Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 1
- DDUHZTYCFQRHIY-UHFFFAOYSA-N Negwer: 6874 Natural products COC1=CC(=O)CC(C)C11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 DDUHZTYCFQRHIY-UHFFFAOYSA-N 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 229930189077 Rifamycin Natural products 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 108010059993 Vancomycin Proteins 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 229960004821 amikacin Drugs 0.000 description 1
- LKCWBDHBTVXHDL-RMDFUYIESA-N amikacin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O1)O)NC(=O)[C@@H](O)CCN)[C@H]1O[C@H](CN)[C@@H](O)[C@H](O)[C@H]1O LKCWBDHBTVXHDL-RMDFUYIESA-N 0.000 description 1
- 229940009444 amphotericin Drugs 0.000 description 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940124350 antibacterial drug Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 230000005975 antitumor immune response Effects 0.000 description 1
- 229960005397 arbekacin Drugs 0.000 description 1
- MKKYBZZTJQGVCD-XTCKQBCOSA-N arbekacin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O1)O)NC(=O)[C@@H](O)CCN)[C@H]1O[C@H](CN)CC[C@H]1N MKKYBZZTJQGVCD-XTCKQBCOSA-N 0.000 description 1
- 229960004099 azithromycin Drugs 0.000 description 1
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 description 1
- WZPBZJONDBGPKJ-VEHQQRBSSA-N aztreonam Chemical compound O=C1N(S([O-])(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(=N/OC(C)(C)C(O)=O)\C1=CSC([NH3+])=N1 WZPBZJONDBGPKJ-VEHQQRBSSA-N 0.000 description 1
- 229960003644 aztreonam Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 229940022399 cancer vaccine Drugs 0.000 description 1
- 238000009566 cancer vaccine Methods 0.000 description 1
- 229960003669 carbenicillin Drugs 0.000 description 1
- FPPNZSSZRUTDAP-UWFZAAFLSA-N carbenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C(O)=O)C1=CC=CC=C1 FPPNZSSZRUTDAP-UWFZAAFLSA-N 0.000 description 1
- 229960003719 cefdinir Drugs 0.000 description 1
- RTXOFQZKPXMALH-GHXIOONMSA-N cefdinir Chemical compound S1C(N)=NC(C(=N\O)\C(=O)N[C@@H]2C(N3C(=C(C=C)CS[C@@H]32)C(O)=O)=O)=C1 RTXOFQZKPXMALH-GHXIOONMSA-N 0.000 description 1
- AFZFFLVORLEPPO-UVYJNCLZSA-N cefditoren pivoxil Chemical compound S([C@@H]1[C@@H](C(N1C=1C(=O)OCOC(=O)C(C)(C)C)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1\C=C/C=1SC=NC=1C AFZFFLVORLEPPO-UVYJNCLZSA-N 0.000 description 1
- 229960002142 cefditoren pivoxil Drugs 0.000 description 1
- 229960002129 cefixime Drugs 0.000 description 1
- OKBVVJOGVLARMR-QSWIMTSFSA-N cefixime Chemical compound S1C(N)=NC(C(=N\OCC(O)=O)\C(=O)N[C@@H]2C(N3C(=C(C=C)CS[C@@H]32)C(O)=O)=O)=C1 OKBVVJOGVLARMR-QSWIMTSFSA-N 0.000 description 1
- JSDXOWVAHXDYCU-VXSYNFHWSA-N cefminox Chemical compound S([C@@H]1[C@@](C(N1C=1C(O)=O)=O)(NC(=O)CSC[C@@H](N)C(O)=O)OC)CC=1CSC1=NN=NN1C JSDXOWVAHXDYCU-VXSYNFHWSA-N 0.000 description 1
- 229960004261 cefotaxime Drugs 0.000 description 1
- GPRBEKHLDVQUJE-VINNURBNSA-N cefotaxime Chemical compound N([C@@H]1C(N2C(=C(COC(C)=O)CS[C@@H]21)C(O)=O)=O)C(=O)/C(=N/OC)C1=CSC(N)=N1 GPRBEKHLDVQUJE-VINNURBNSA-N 0.000 description 1
- DKOQGJHPHLTOJR-WHRDSVKCSA-N cefpirome Chemical compound N([C@@H]1C(N2C(=C(C[N+]=3C=4CCCC=4C=CC=3)CS[C@@H]21)C([O-])=O)=O)C(=O)\C(=N/OC)C1=CSC(N)=N1 DKOQGJHPHLTOJR-WHRDSVKCSA-N 0.000 description 1
- 229960000466 cefpirome Drugs 0.000 description 1
- 229960002588 cefradine Drugs 0.000 description 1
- 229960004755 ceftriaxone Drugs 0.000 description 1
- VAAUVRVFOQPIGI-SPQHTLEESA-N ceftriaxone Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C(=O)NN1C VAAUVRVFOQPIGI-SPQHTLEESA-N 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 229940106164 cephalexin Drugs 0.000 description 1
- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 description 1
- RDLPVSKMFDYCOR-UEKVPHQBSA-N cephradine Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CCC=CC1 RDLPVSKMFDYCOR-UEKVPHQBSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 229960003405 ciprofloxacin Drugs 0.000 description 1
- 229960002626 clarithromycin Drugs 0.000 description 1
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 description 1
- 229960001127 colistin sulfate Drugs 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- YFAGHNZHGGCZAX-JKIFEVAISA-N dicloxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=C(Cl)C=CC=C1Cl YFAGHNZHGGCZAX-JKIFEVAISA-N 0.000 description 1
- 229960001585 dicloxacillin Drugs 0.000 description 1
- PXEDJBXQKAGXNJ-QTNFYWBSSA-L disodium L-glutamate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](N)CCC([O-])=O PXEDJBXQKAGXNJ-QTNFYWBSSA-L 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- IVTMALDHFAHOGL-UHFFFAOYSA-N eriodictyol 7-O-rutinoside Natural products OC1C(O)C(O)C(C)OC1OCC1C(O)C(O)C(O)C(OC=2C=C3C(C(C(O)=C(O3)C=3C=C(O)C(O)=CC=3)=O)=C(O)C=2)O1 IVTMALDHFAHOGL-UHFFFAOYSA-N 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 229960000741 erythromycin ethylsuccinate Drugs 0.000 description 1
- NSYZCCDSJNWWJL-YXOIYICCSA-N erythromycin ethylsuccinate Chemical compound O1[C@H](C)C[C@H](N(C)C)[C@@H](OC(=O)CCC(=O)OCC)[C@@H]1O[C@H]1[C@@](O)(C)C[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@](C)(O)[C@@H](CC)OC(=O)[C@H](C)[C@@H](O[C@@H]2O[C@@H](C)[C@H](O)[C@](C)(OC)C2)[C@@H]1C NSYZCCDSJNWWJL-YXOIYICCSA-N 0.000 description 1
- 238000000556 factor analysis Methods 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 210000003495 flagella Anatomy 0.000 description 1
- 229960004273 floxacillin Drugs 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 229960002867 griseofulvin Drugs 0.000 description 1
- DDUHZTYCFQRHIY-RBHXEPJQSA-N griseofulvin Chemical compound COC1=CC(=O)C[C@@H](C)[C@@]11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 DDUHZTYCFQRHIY-RBHXEPJQSA-N 0.000 description 1
- 230000000899 immune system response Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 229940088592 immunologic factor Drugs 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229960004144 josamycin Drugs 0.000 description 1
- XJSFLOJWULLJQS-NGVXBBESSA-N josamycin Chemical compound CO[C@H]1[C@H](OC(C)=O)CC(=O)O[C@H](C)C\C=C\C=C\[C@H](O)[C@H](C)C[C@H](CC=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](N(C)C)[C@H](O[C@@H]2O[C@@H](C)[C@H](OC(=O)CC(C)C)[C@](C)(O)C2)[C@@H](C)O1 XJSFLOJWULLJQS-NGVXBBESSA-N 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- JCQLYHFGKNRPGE-FCVZTGTOSA-N lactulose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 JCQLYHFGKNRPGE-FCVZTGTOSA-N 0.000 description 1
- 229960000511 lactulose Drugs 0.000 description 1
- 229960003376 levofloxacin Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229960005287 lincomycin Drugs 0.000 description 1
- OJMMVQQUTAEWLP-KIDUDLJLSA-N lincomycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@@H](C)O)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 OJMMVQQUTAEWLP-KIDUDLJLSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 229940041033 macrolides Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229960002260 meropenem Drugs 0.000 description 1
- DMJNNHOOLUXYBV-PQTSNVLCSA-N meropenem Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)S[C@@H]1CN[C@H](C(=O)N(C)C)C1 DMJNNHOOLUXYBV-PQTSNVLCSA-N 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- 229960000282 metronidazole Drugs 0.000 description 1
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 235000013923 monosodium glutamate Nutrition 0.000 description 1
- ZESIAEVDVPWEKB-ORCFLVBFSA-N n-[(2s)-4-amino-1-[[(2s,3r)-1-[[(2s)-4-amino-1-oxo-1-[[(3s,6s,9s,12s,15r,18s,21s)-6,9,18-tris(2-aminoethyl)-3-[(1r)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-h Chemical compound OS(O)(=O)=O.OS(O)(=O)=O.CC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O.CCC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O ZESIAEVDVPWEKB-ORCFLVBFSA-N 0.000 description 1
- 229940117269 nivolumab injection Drugs 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 229960001180 norfloxacin Drugs 0.000 description 1
- OGJPXUAPXNRGGI-UHFFFAOYSA-N norfloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 OGJPXUAPXNRGGI-UHFFFAOYSA-N 0.000 description 1
- 239000006191 orally-disintegrating tablet Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 229960002621 pembrolizumab Drugs 0.000 description 1
- 239000006041 probiotic Substances 0.000 description 1
- 235000018291 probiotics Nutrition 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- FDRQPMVGJOQVTL-UHFFFAOYSA-N quercetin rutinoside Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 FDRQPMVGJOQVTL-UHFFFAOYSA-N 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- BTVYFIMKUHNOBZ-QXMMDKDBSA-N rifamycin s Chemical class O=C1C(C(O)=C2C)=C3C(=O)C=C1NC(=O)\C(C)=C/C=C\C(C)C(O)C(C)C(O)C(C)C(OC(C)=O)C(C)C(OC)\C=C/OC1(C)OC2=C3C1=O BTVYFIMKUHNOBZ-QXMMDKDBSA-N 0.000 description 1
- 229940081192 rifamycins Drugs 0.000 description 1
- WDZCUPBHRAEYDL-GZAUEHORSA-N rifapentine Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C(O)=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N(CC1)CCN1C1CCCC1 WDZCUPBHRAEYDL-GZAUEHORSA-N 0.000 description 1
- 229960005224 roxithromycin Drugs 0.000 description 1
- IKGXIBQEEMLURG-BKUODXTLSA-N rutin Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@@H]1OC[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 IKGXIBQEEMLURG-BKUODXTLSA-N 0.000 description 1
- ALABRVAAKCSLSC-UHFFFAOYSA-N rutin Natural products CC1OC(OCC2OC(O)C(O)C(O)C2O)C(O)C(O)C1OC3=C(Oc4cc(O)cc(O)c4C3=O)c5ccc(O)c(O)c5 ALABRVAAKCSLSC-UHFFFAOYSA-N 0.000 description 1
- 235000005493 rutin Nutrition 0.000 description 1
- 229960004555 rutoside Drugs 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229940073490 sodium glutamate Drugs 0.000 description 1
- ZPCCSZFPOXBNDL-RSMXASMKSA-N spiramycin II Chemical compound O([C@H]1/C=C/C=C/C[C@@H](C)OC(=O)C[C@H]([C@@H]([C@H]([C@@H](CC=O)C[C@H]1C)O[C@H]1[C@@H]([C@H]([C@H](O[C@@H]2O[C@@H](C)[C@H](O)[C@](C)(O)C2)[C@@H](C)O1)N(C)C)O)OC)OC(C)=O)[C@H]1CC[C@H](N(C)C)[C@H](C)O1 ZPCCSZFPOXBNDL-RSMXASMKSA-N 0.000 description 1
- 229950006796 spiramycin ii Drugs 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229960005404 sulfamethoxazole Drugs 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- JLKIGFTWXXRPMT-UHFFFAOYSA-N sulphamethoxazole Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 JLKIGFTWXXRPMT-UHFFFAOYSA-N 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 229940066453 tecentriq Drugs 0.000 description 1
- 229960003250 telithromycin Drugs 0.000 description 1
- LJVAJPDWBABPEJ-PNUFFHFMSA-N telithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)[C@@H](C)C(=O)O[C@@H]([C@]2(OC(=O)N(CCCCN3C=C(N=C3)C=3C=NC=CC=3)[C@@H]2[C@@H](C)C(=O)[C@H](C)C[C@@]1(C)OC)C)CC)[C@@H]1O[C@H](C)C[C@H](N(C)C)[C@H]1O LJVAJPDWBABPEJ-PNUFFHFMSA-N 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229940040944 tetracyclines Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 1
- 229960003165 vancomycin Drugs 0.000 description 1
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 1
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/745—Bifidobacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/7036—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/742—Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K2035/11—Medicinal preparations comprising living procariotic cells
- A61K2035/115—Probiotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Definitions
- This application relates to an anti-tumor composition, and more specifically to the combined use of Bifidobacterium longum and immune checkpoint inhibitors.
- Cure cancer has always been a major problem in the medical field. Traditional chemotherapy, radiotherapy and other treatment methods will bring greater side effects and pain to patients. In recent years, cancer immunotherapy has shown amazing curative effects in hematomas and some solid tumors, and it brings less side effects to patients, and brings great hope to human beings to cure cancer.
- Tumor immunotherapy is the trick of identifying and destroying tumor cells, so that the body can restore normal anti-tumor immune response, which can control and eliminate a variety of tumors.
- Tumor immunotherapy mainly includes five types: (1) therapeutic antibodies; (2) cancer vaccines; (3) cell therapy, that is, CAR-T therapy; (4) immunomodulators; (5) immune checkpoint inhibitors.
- the activity of the human immune system is regulated by costimulatory molecules, which are immune checkpoints.
- immune checkpoints When antigen recognition occurs, other molecules interact with immune cells and target cell surface molecules to determine the balance of interactions. If the signal is largely positive, immune cells will be activated and attack the antigen presented by the target cell. Conversely, if the signal is negative, immune cells will be inactivated, this inactivation is sometimes permanent, and the antigen is recognized as a normal/self antigen.
- Cancer-related immune checkpoints that have been relatively well-studied include CTLA-4, PD-1 and PD-L1. Immune checkpoint inhibitors are some monoclonal antibodies developed for the corresponding immune checkpoints.
- immune checkpoint inhibitors include monoclonal antibodies that target programmed death protein 1 (PD-1) and its ligand (PD-L1).
- PD-1 antibody is very effective in blocking advanced melanoma, non-small cell lung cancer and renal cell carcinoma, and has made a major breakthrough in the treatment of tumors.
- immune checkpoint inhibitors due to the complex pathogenesis of tumors, the large differences in individual patients, and the influence of environmental factors, immune checkpoint inhibitors currently only have an effect on about 25% of patients.
- Bifidobacterium longum and immune checkpoint inhibitors can effectively inhibit various tumors, including but not limited to colon cancer, lung cancer, breast cancer, melanoma, kidney cancer, and urothelial cancer and many more.
- an anti-tumor composition which includes:
- the Bifidobacterium longum is Bifidobacterium longum 6-1.
- the Bifidobacterium longum is combined with other bacteria (such as Bifidobacterium, Lactobacillus, Clostridium, Enterococcus faecium, Prevotella faecalis, Rumencoccus).
- other bacteria such as Bifidobacterium, Lactobacillus, Clostridium, Enterococcus faecium, Prevotella faecalis, Rumencoccus).
- the Bifidobacterium longum and the immune checkpoint inhibitor are mixed together to prepare a single preparation, or physically separated and used separately.
- the Bifidobacterium longum is in the form of oral or injection.
- the anti-tumor composition further includes antibiotics.
- the tumor is selected from colon cancer, lung cancer, stomach cancer, liver cancer, head and neck cancer, cervical cancer, breast cancer, lymphoma, breast cancer, melanoma, kidney cancer, or urothelial cancer.
- the application also provides the use of Bifidobacterium longum in the preparation of drugs for treating tumors.
- the Bifidobacterium longum is used in combination with an immune checkpoint inhibitor preparation.
- the use is to improve the effect of immune checkpoint inhibitors in suppressing tumors.
- the tumors are selected from colon cancer, lung cancer, gastric cancer, liver cancer, head and neck cancer, cervical cancer, breast cancer, and lymphatic cancer. Cancer, breast cancer, melanoma, kidney cancer, or urothelial cancer.
- Figure 1 depicts the effect of antibiotics destroying intestinal flora on tumor growth and anti-mPD-1 treatment in MC38 tumor-bearing mice.
- Figure 2 depicts the effects of single injection of anti-mPD-1 and single oral administration of Bifidobacterium longum 6-1 on tumor growth in MC38 tumor-bearing mice.
- Figure 3 depicts the combined use of anti-m PD-1 and Bifidobacterium longum 6-1 on the tumor treatment effect of MC38 tumor-bearing mice.
- Figure 4 depicts the difference in tumor treatment effects of different probiotics and anti-m PD-1 on MC38 tumor-bearing mice.
- Figure 5 depicts the average number of CD3 cells in MC38 tumor-bearing mice when anti-m PD-1 was injected alone and in combination with Bifidobacterium longum 6-1.
- Figure 6 depicts the number of tumor-infiltrating CD8 T cells in MC38 tumor-bearing mice when anti-m PD-1 was injected alone and used in combination with Bifidobacterium longum 6-1.
- Figure 7 depicts the therapeutic effect of anti-m PD-1 injection alone and in combination with Bifidobacterium longum 6-1 on 4T1 tumors.
- Figure 8 depicts the therapeutic effect of anti-m PD-1 injection alone and combined with Bifidobacterium longum 6-1 on LLC1 tumors.
- percentage (%) or parts refer to the weight percentage or parts by weight relative to the composition.
- the sum of the parts of each component in the composition may be 100 parts by weight.
- the numerical range "a-b” represents an abbreviated representation of any combination of real numbers between a and b, where both a and b are real numbers.
- the numerical range "0-5" means that all real numbers between "0-5" have been listed in this article, and "0-5" is only an abbreviation of these numerical combinations.
- the integer value range "a-b” represents an abbreviated representation of any combination of integers between a and b, where both a and b are integers.
- the integer value range "1-N" means 1, 2...N, where N is an integer.
- “combination thereof” means a multi-component mixture of the respective elements, for example, two, three, four, and up to the largest possible multi-component mixtures.
- the percentages (including weight percentages) in the present invention are based on the total weight of the composition.
- the “range” disclosed herein takes the form of the lower limit and the upper limit. There can be one or more lower limits, and one or more upper limits, respectively.
- the given range is limited by selecting a lower limit and an upper limit.
- the selected lower and upper limits define the boundaries of the particular range. All ranges that can be defined in this way are inclusive and combinable, that is, any lower limit can be combined with any upper limit to form a range.
- the ranges of 60-120 and 80-110 are listed for specific parameters, and the ranges of 60-110 and 80-120 are also expected.
- the minimum range values 1 and 2 are listed, and if the maximum range values 3, 4, and 5 are listed, the following ranges can all be expected: 1-3, 1-4, 1-5, 2- 3, 2-4, and 2-5.
- the ratio or weight of each component refers to the dry weight.
- Bifidobacterium longum includes an active ingredient derived from Bifidobacterium longum, or a strain whose sequence identification result is at least 99% similar to that of Bifidobacterium longum.
- the long-form Bifidobacterium described in the present application can be obtained through commercial channels, and can also be obtained through existing technologies.
- the Bifidobacterium longum can be obtained according to CN103830278A, CN103131647A, CN101244090A, CN101244089A, CN1223865A or US6368591.
- the long-form Bifidobacterium of the present invention is conventional in the art and can be isolated from healthy adult feces. For example, it has been disclosed in the authorized US6368591, in which the deposit number of Bifidobacterium longum is CCTCC M98003.
- Bifidobacterium longum is an anaerobic bacteria with positive Gram stain, uneven coloration, no spores, no capsules, no flagella, and the bacteria are straight or curved, and may appear "Y" or "V" The bifurcated, rod-shaped and many other forms.
- the Bifidobacterium longum is Bifidobacterium longum (6-1).
- the Bifidobacterium longum may be in the form of Bifidobacterium longum powder.
- the Bifidobacterium longum bacteria powder comprises Bifidobacterium and a first protective agent, and the first protective agent contains 8-50% skimmed milk powder, 0.01-10% sodium glutamate, and isolactose. 8-50%, Vc-Na 0.01-5%, starch 4-30%, based on the total weight of the first protective agent.
- the Bifidobacterium longum powder can be made into various suitable dosage forms, such as oral liquids, tablets, capsules, orally disintegrating tablets, freeze-dried powders and the like.
- the dosage form is a capsule.
- the dosage form is a tablet.
- the dosage form is preferably a freeze-dried bacterial agent, and the number of viable bacteria therein is preferably 10 10 CFU/g.
- the Bifidobacterium longum can also be combined with other strains (including but not limited to Bifidobacterium, Lactobacillus, Clostridium, Enterococcus faecium, Prevotella faecalis, Rumencoccus, etc. )use together.
- other strains including but not limited to Bifidobacterium, Lactobacillus, Clostridium, Enterococcus faecium, Prevotella faecalis, Rumencoccus, etc.
- the immune checkpoint inhibitor used in this application can be any commercially available product, such as PD-1 inhibitor, PD-L1 inhibitor, CTLA-4 inhibitor, etc.
- the immune checkpoint inhibitor includes Keytruda, Tecentriq, Nivolumab Injection, Bavencio (Avelumab), Tuoyi (Special) Riprolizumab injection).
- the Bifidobacterium longum and the immune checkpoint inhibitor can be mixed together to prepare a single preparation and used together, or they can be physically separated and used separately. In an example of the present application, the Bifidobacterium longum and the immune checkpoint inhibitor are physically separated and used separately. In another example of the present application, the Bifidobacterium longum may be administered to the patient before the immune checkpoint inhibitor is administered. Generally, the Bifidobacterium longum can be administered to the patient in any suitable manner (including but not limited to oral, injection, etc.). The immune checkpoint inhibitor can be administered to the patient in any suitable manner (including but not limited to oral, injection, etc.). The method of using the Bifidobacterium longum or immune checkpoint inhibitor is routine in the art, and can be directly determined by a person of ordinary skill in the art according to the description in the specification and combined with the existing technology.
- the anti-tumor composition may also include antibiotics.
- the antibiotic may be any suitable antibiotic, such as but not limited to quinolone antibiotics, ⁇ -lactam antibiotics, macrolides, aminoglycoside antibiotics, and the like.
- the antibiotics include but are not limited to ⁇ -lactam antibiotics (such as penicillin, ampicillin, carbenicillin, methicillin, benzoxacillin, dicloxacillin, flucloxacillin, cefradine , Cefotaxime, cephalexin, ceftriaxone, cefpirome, cefixime, cefditoren pivoxil, cefdinir, cefbutene, cefpacime, imipenem, aztreonam, cefminox Sodium, Biampenem, Imipenem, Meropenem, etc.); Macrolide antibiotics (such as erythromycin, leucomycin, roxithromycin, erythromycin ethylsuccinate, azithromycin, clarithromycin, acetyl Spiramycin, meleumycin, midemycin, josamycin, telithromycin, etc.); aminoglycoside antibiotics (streptomycin,
- the antibiotic can be packaged separately from other components and administered separately.
- the anti-tumor composition further includes instructions that describe the administration of Bifidobacterium longum for a period of time (for example, 1-10 days), and then administration of the PD-1 inhibitor for a period of time ( For example, 10-100 days).
- the dose range of Bifidobacterium longum is 10 4 -10 13 CFU/person/day
- the dose range of the immune checkpoint inhibitor 0.5-10 mg/kg.
- the instructions also describe the administration of antibiotics for a period of time (for example, 1-3 days) before the administration of Bifidobacterium longum and PD-1 inhibitor.
- the dose range of antibiotics 1-500 mg/kg.
- the anti-tumor composition of the present application can effectively treat various tumors, especially (but not limited to) colon cancer, lung cancer, breast cancer, melanoma, kidney cancer, urothelial cancer and the like.
- Another aspect of the present application provides the use of Bifidobacterium longum in the preparation of drugs for treating tumors.
- the Bifidobacterium longum can be combined with immune checkpoint inhibitors to inhibit the growth of tumors (such as colon cancer, lung cancer, breast cancer, melanoma, kidney cancer, urothelial cancer, etc.).
- tumors such as colon cancer, lung cancer, breast cancer, melanoma, kidney cancer, urothelial cancer, etc.
- the inventor found that when the patient uses antibiotics, the effect of immune checkpoint inhibitors in inhibiting tumor growth is limited, but the administration of Bifidobacterium longum before or at the same time can effectively increase the immune checkpoint inhibitors to inhibit tumors. Effect.
- Another aspect of the application provides the use of Bifidobacterium longum in the treatment of tumors.
- the use includes inhibiting tumor growth.
- the Bifidobacterium longum can be used in combination with an immune checkpoint inhibitor.
- the tumors include, but are limited to, colon cancer, lung cancer, breast cancer, melanoma, kidney cancer, urothelial cancer, and the like.
- the PD-1 inhibitor was purchased from Yikang (Beijing) Pharmaceutical Technology Co., Ltd., at a concentration of 7.09 mg/mL, and stored at 2-8°C in the dark. Add an appropriate amount of phosphate buffered saline solution and mix to a solution of the specified concentration.
- Ampicillin (Ampicillin) was purchased from Anfeng Anfengtang Animal Pharmaceutical Co., Ltd.
- Streptomycin Streptomycin
- Solarbio Company Streptomycin (Streptomycin) was purchased from Solarbio Company
- Colistin sulfate soluble powder Coldbio Company
- MC38 tumor cells were purchased from Ruting Biotechnology (Beijing) Co., Ltd., using fire-extinguished 10% fetal bovine serum, 100U/mL penicillin, 100 ⁇ g/mL streptomycin, and 2mM glutamine in DMEM medium at 37°C, 5
- the tumor cells are cultured in a %CO 2 incubator, and the cells are divided into bottles for passage every 3 days or so, and the tumor cells in the logarithmic growth phase are used for inoculation of tumors in vivo.
- Mouse breast cancer 4T1 cells (ATCC, catalog number: CRL-2539), LLC1 lung cancer cells (purchased from Shanghai Institutes for Biological Sciences).
- Bifidobacterium longum 6-1 is Bifidobacterium longum 6-1 (CCTCC M98003).
- Tumor volume Use a vernier caliper to measure the tumor volume three times a week to measure the long and short diameters of the tumor.
- mice Forty-eight male C57BL/6J mice aged 6-8 weeks, after adapting to the environment for one week, were randomly divided into 4 groups according to their body weight, each with 12 mice, respectively: Group 1 (no antibiotic treatment, blank, ip), 2 Group (no antibiotic treatment, anti-mPD-1, 10mg/kg, ip), group 3 (antibiotic treatment, blank, ip), group 4 (antibiotic treatment, anti-mPD-1, 10mg/kg, ip) .
- Antibiotic treatment is to use broad-spectrum antibiotic Ampicillin (1mg/mL) + colistin (1mg/mL) + streptomycin (5mg/mL) drinking water for 5 days.
- Mice in groups 2 and 4 were injected with anti-mPD-1 on the 4th day after tumor cell inoculation, once every 4 days, for a total of 4 injections. The mice were euthanized on the 19th day after tumor inoculation.
- MC38 tumor cells were purchased from Ruting Biotechnology Co., Ltd., and used DMEM medium containing inactivated 10% fetal bovine serum, 100U/mL penicillin, 100 ⁇ g/mL streptomycin and 2mM glutamine at 37°C, 5% The tumor cells are cultured in a CO 2 incubator, and the cells are divided into bottles for passage every 3 days or so, and the tumor cells in the logarithmic growth phase are used for inoculation of tumors in vivo.
- the test results are shown in Figure 1.
- the results showed that antibiotic treatment destroyed the intestinal flora of mice, accelerated tumor growth in mice, increased tumor volume, and had a certain degree of impact on the anti-m PD-1 treatment effect.
- the intestinal flora affects the growth of tumors in mice and the therapeutic effect of anti-m s PD-1.
- mice Thirty-six male C57BL/6J mice (20-26g, SPF grade) 6-8 weeks old. After one week of adaptation to the environment, they were randomly divided into 3 groups according to their body weight, the first group (antibiotic treatment, blank, ip), the second group (Antibiotic treatment, anti-mPD-1, 10mg/kg, ip), group 3 (antibiotic treatment, Bifidobacterium longum 6-1, po).
- Antibiotic treatment is to use broad-spectrum antibiotic Ampicillin (1mg/mL) + colistin (1mg/mL) + streptomycin (5mg/mL) drinking water for 5 days.
- mice in the third group were given lyophilized samples of Bifidobacterium longum at an intragastric concentration of 1.0 ⁇ 10 8 CFU/mouse/day. After continuous gavage for 2 weeks, mice in all groups were inoculated with PBS-resuspended MC38 tumor cells at a concentration of 1 ⁇ 10 7 cells/mL, and inoculated into the right flank of experimental animals subcutaneously, 100 ⁇ L/mouse.
- anti-mPD-1 was injected on the 4th day after tumor cell inoculation, once every 4 days, for a total of 4 injections. The mice were euthanized on the 19th day after tumor inoculation.
- MC38 tumor cells were purchased from Rutin Biotechnology Co., Ltd., and used DMEM medium containing inactivated 10% fetal bovine serum, 100U/mL penicillin, 100 ⁇ g/mL streptomycin and 2mM glutamine at 37°C, 5% The tumor cells are cultured in a CO2 incubator, and the cells are divided into bottles for passage every 3 days or so, and the tumor cells in the logarithmic growth phase are used for inoculation of tumors in vivo.
- mice Thirty-six male C57BL/6J mice (20-26g, SPF grade) 6-8 weeks old. After one week of adaptation to the environment, they were randomly divided into 3 groups according to their body weight, the first group (antibiotic treatment, blank, ip), the second group (Antibiotic treatment, anti-mPD-1, 10mg/kg, ip), group 3 (antibiotic treatment, Bifidobacterium longum 6-1, po, anti-mPD-1, 10mg/kg, ip).
- Antibiotic treatment is to use broad-spectrum antibiotic Ampicillin (1mg/mL) + colistin (1mg/mL) + streptomycin (5mg/mL) drinking water for 5 days.
- mice in the third group were given the freeze-dried samples of Bifidobacterium longum at an intragastric concentration of 1.0 ⁇ 10 8 CFU/mouse/day for 2 weeks.
- Mice in all groups were inoculated with MC38 tumor cells resuspended in PBS at a concentration of 1 ⁇ 10 7 cells/mL, and inoculated subcutaneously in the right flank of experimental animals, 100 ⁇ L/mouse.
- the mice in groups 2 and 3 were injected with anti-mPD-1 on the 4th day after tumor cell inoculation, once every 4 days, for a total of 4 injections. The mice were euthanized on the 19th day after tumor inoculation.
- Cultivation of tumor cells Use DMEM medium containing inactivated 10% fetal bovine serum, 100 U/mL penicillin, 100 ⁇ g/mL streptomycin, and 2 mM glutamine in an incubator at 37°C and 5% CO 2 Tumor cells are divided into bottles and passaged every 3 days or so after the cells are full, and the tumor cells in the logarithmic growth phase are used for tumor inoculation in vivo.
- mice Forty-eight male C57BL/6J mice (20-26g, SPF grade) 6-8 weeks old, after adapting to the environment for one week, they were randomly divided into 4 groups according to their body weight, the first group (antibiotic treatment, blank, ip), the second group ( Antibiotic treatment, Bifidobacterium longum 6-1, po, anti-mPD-1, 10mg/kg, ip), group 3 (antibiotic treatment, Bifidobacterium longum BL2 (fecal samples of healthy people), po, anti-mPD-1, 10mg/kg, ip), group 4 (antibiotic treatment, Bifidobacterium longum BL3 (fecal samples of healthy people), po, anti-mPD-1, 10mg/kg, ip).
- the first group antibiotic treatment, blank, ip
- the second group Antibiotic treatment, Bifidobacterium longum 6-1, po, anti-mPD-1, 10mg/kg, ip
- group 3 antibiotic treatment,
- Antibiotic treatment is to use broad-spectrum antibiotic Ampicillin (1mg/mL) + colistin (1mg/mL) + streptomycin (5mg/mL) drinking water for 5 days.
- the mice in groups 2-4 were given the freeze-dried samples of Bifidobacterium longum at an intragastric concentration of 1.0 ⁇ 10 8 CFU/mouse/day, after continuous intragastric administration for 2 weeks.
- Mice in all groups were inoculated with MC38 tumor cells resuspended in PBS at a concentration of 1 ⁇ 10 7 cells/mL, and inoculated subcutaneously in the right flank of experimental animals, 100 ⁇ L/mouse.
- the mice in groups 2-4 were injected with anti-mPD-1 on the 4th day after tumor cell inoculation, once every 4 days, for a total of 4 injections. The mice were euthanized on the 19th day after tumor inoculation.
- Cultivation of MC38 tumor cells Use DMEM medium containing inactivated 10% fetal bovine serum, 100U/mL penicillin, 100 ⁇ g/mL streptomycin, and 2mM glutamine in an incubator at 37°C and 5% CO2 Tumor cells are divided into bottles and passaged every 3 days or so after the cells are full, and the tumor cells in the logarithmic growth phase are used for tumor inoculation in vivo.
- mice in Example 3 were euthanized on the 19th day after tumor inoculation.
- Flow cytometry was used to detect CD3, CD4, CD8, FOXP3, CD25, CXCR3, Gata3, Granzyme B, CD69, PD-1, CTLA in tumor cells.
- Immune factor analysis includes TNF- ⁇ , IL-17, IL-13, IL-12p70, IL-10, IL-6, IL-5, IL-4, IL-2, IL-1b, IFNy, GM-CSF, G-CSF, M-CSF, MIG, IP-10, MIP1b and MAC-1.
- mice in Example 3 were euthanized on the 19th day after tumor inoculation. Flow cytometry was used to detect CD3, CD4, CD8, FOXP3, CD25, CXCR3, Gata3, Granzyme B, CD69, PD-1, CTLA in tumor cells. -4, and CD11b, MHCII, CD206, CD40, CSF1R, PD-L1, Gr-1.
- the experimental results are shown in Figure 6. The results showed that compared with the injection of anti-m PD-1 alone, the combined treatment of oral Bifidobacterium longum 6-1 and anti-m PD-1 injection significantly increased the number of tumor-infiltrated CD8 T cells, and the immune system of mice The response is enhanced. Compared with the antibiotic treatment group in the table, P ⁇ 0.05 indicates a significant difference, **P ⁇ 0.01.
- mice Forty-eight male C57BL/6J mice (20-26g, SPF grade) 6-8 weeks old, after one week of adaptation to the environment, they were randomly divided into 4 groups according to their body weight, the first group (blank, ip), the second group (anti-mPD) -1, 10mg/kg, ip), group 3 (Bifidobacterium longum 6-1, po), group 4 (Bifidobacterium longum 6-1, po, anti-mPD-1, 10mg/kg , Ip).
- the mice in groups 3 and 4 were intragastrically administered with freeze-dried samples of Bifidobacterium longum 6-1 at a concentration of 1.0 ⁇ 10 8 CFU/mouse/day.
- Mice in groups 2 and 4 were injected with anti-mPD-1 on the 4th day after tumor cell inoculation, once every 4 days, for a total of 4 injections. The mice were euthanized on the 19th day after tumor inoculation.
- mice Thirty-six male C57BL/6J mice (20-26g, SPF grade) 6-8 weeks old. After one week of adaptation to the environment, they were randomly divided into 3 groups according to their body weight, the first group (blank, ip) and the second group (anti-mPD). -1, 10mg/kg, ip), group 3 (Bifidobacterium longum 6-1, po, anti-mPD-1, 10mg/kg, ip). The mice in the third group were intragastrically administered with a freeze-dried sample of Bifidobacterium longum 6-1 at a concentration of 1.0 ⁇ 10 8 CFU/mouse/day.
- the mice in groups 2 and 3 were injected with anti-mPD-1 on the 4th day after tumor cell inoculation, once every 4 days, for a total of 4 injections.
- the mice were euthanized on the 19th day after tumor inoculation.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Oncology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Endocrinology (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Description
Claims (10)
- 一种抗肿瘤组合物,其包括:(A)长型双歧杆菌;以及(B)免疫检查点抑制剂。
- 如权利要求1所述的抗肿瘤组合物,其特征在于,所述长型双歧杆菌是长型双歧杆菌6-1。
- 如权利要求1或2所述的抗肿瘤组合物,其特征在于,所述长型双歧杆菌与其他菌(如双歧杆菌、乳杆菌、梭菌、屎肠球菌、粪便普雷沃氏菌、瘤胃球菌)组合在一起。
- 如权利要求1或2所述的抗肿瘤组合物,其特征在于,所述长型双歧杆菌和免疫检查点抑制剂混合在一起制备单一制剂,或者物理上分离分别使用。
- 如权利要求1或2所述的抗肿瘤组合物,其特征在于,所述长型双歧杆菌是口服或注射剂型。
- 如权利要求1或2所述的抗肿瘤组合物,其特征在于,所述抗肿瘤组合物还包括抗生素。
- 如权利要求1或2所述的抗肿瘤组合物,其特征在于,所述肿瘤选自结肠癌、肺癌、胃癌、肝癌、头颈癌、***、乳腺癌、淋巴癌、乳腺癌、黑色素瘤、肾癌或尿路上皮癌。
- 长型双歧杆菌在制备***的药物中的用途。
- 如权利要求8所述的用途,其特征在于,所述长型双歧杆菌与免疫检查点抑制剂制剂联合使用。
- 如权利要求8或9所述的用途,其特征在于,所述用途是提高免疫检查点抑制剂抑制肿瘤的效果,优选地,所述肿瘤选自结肠癌、肺癌、胃癌、肝癌、头颈癌、***、乳腺癌、淋巴癌、乳腺癌、黑色素瘤、肾癌或尿路上皮癌。
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA3173276A CA3173276A1 (en) | 2020-02-27 | 2021-03-01 | Anti-tumor composition comprising bifidobacterium longum 6-1 and an immune checkpoint inhibitor |
AU2021226553A AU2021226553A1 (en) | 2020-02-27 | 2021-03-01 | Anti-tumor composition |
KR1020227029973A KR20220133282A (ko) | 2020-02-27 | 2021-03-01 | 항종양 조성물 |
JP2022576574A JP2023516101A (ja) | 2020-02-27 | 2021-03-01 | 抗腫瘍組成物 |
EP21760816.5A EP4112065A4 (en) | 2020-02-27 | 2021-03-01 | ANTI-TUMOOR COMPOSITION |
US17/904,953 US20230118958A1 (en) | 2020-02-27 | 2021-03-01 | Anti-tumor composition |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010123739.7A CN111096982B (zh) | 2020-02-27 | 2020-02-27 | 抗肿瘤组合物 |
CN202010123739.7 | 2020-02-27 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2021170138A1 true WO2021170138A1 (zh) | 2021-09-02 |
Family
ID=70427798
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CN2021/078437 WO2021170138A1 (zh) | 2020-02-27 | 2021-03-01 | 抗肿瘤组合物 |
Country Status (8)
Country | Link |
---|---|
US (1) | US20230118958A1 (zh) |
EP (1) | EP4112065A4 (zh) |
JP (1) | JP2023516101A (zh) |
KR (1) | KR20220133282A (zh) |
CN (3) | CN111096982B (zh) |
AU (1) | AU2021226553A1 (zh) |
CA (1) | CA3173276A1 (zh) |
WO (1) | WO2021170138A1 (zh) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114432458A (zh) * | 2022-01-21 | 2022-05-06 | 同济大学 | 一种细菌载药***及其制备方法 |
WO2023116283A1 (zh) * | 2021-12-22 | 2023-06-29 | 苏州普瑞森生物科技有限公司 | 一种抗结直肠肿瘤的乳酸肠球菌及其应用 |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111096982B (zh) * | 2020-02-27 | 2023-09-12 | 上海上药信谊药厂有限公司 | 抗肿瘤组合物 |
CN114392356B (zh) * | 2022-01-12 | 2023-07-25 | 广州知易生物科技有限公司 | 脆弱拟杆菌与免疫检查点抑制剂联用在治疗消化***肿瘤中的应用 |
Citations (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1223865A (zh) | 1998-01-20 | 1999-07-28 | 上海信谊药业有限公司 | 双歧三联活菌制剂及制备方法 |
US6368591B2 (en) | 1998-05-15 | 2002-04-09 | Shanghai Sine Pharmaceutical Corporation Ltd. | Beneficial microbe composition, new protective materials for the microbes, method to prepare the same and uses thereof |
CN101244090A (zh) | 2007-02-16 | 2008-08-20 | 信谊药厂 | 长型双岐杆菌培养基、制剂及其工艺 |
CN101244089A (zh) | 2007-02-16 | 2008-08-20 | 信谊药厂 | 嗜酸乳杆菌/粪肠球菌培养基、制剂及其工艺 |
CN103131647A (zh) | 2011-11-29 | 2013-06-05 | 上海信谊药厂有限公司 | 婴儿双岐杆菌及其制剂 |
CN103830278A (zh) | 2012-11-21 | 2014-06-04 | 上海信谊药厂有限公司 | 活菌冻干粉以及三联活菌制剂的制备方法 |
CN106110322A (zh) * | 2016-07-29 | 2016-11-16 | 安徽瀚海博兴生物技术有限公司 | 一种药物组合物及其在制备治疗癌症药物中的应用 |
CN107847530A (zh) * | 2015-06-01 | 2018-03-27 | 芝加哥大学 | 通过控制共生微生物丛来治疗癌症 |
WO2018226690A1 (en) * | 2017-06-05 | 2018-12-13 | The University Of Chicago | Microbiome biomarkers of immunotherapy responsiveness: diagnostic, prognostic and therapeutic uses thereof |
CN110063970A (zh) * | 2019-04-30 | 2019-07-30 | 上海心脉途医疗科技有限公司 | 与irAE相关的肠道菌群及irAE的治疗和预防方法 |
CN111096982A (zh) * | 2020-02-27 | 2020-05-05 | 上海上药信谊药厂有限公司 | 抗肿瘤组合物 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109758484B (zh) * | 2019-02-18 | 2020-12-25 | 上海交通大学医学院 | 微生物在治疗和/或预防免疫介导的肠道疾病中的应用 |
CN111110852A (zh) * | 2020-02-27 | 2020-05-08 | 上海上药信谊药厂有限公司 | 抗肿瘤组合物 |
-
2020
- 2020-02-27 CN CN202010123739.7A patent/CN111096982B/zh active Active
- 2020-02-27 CN CN202311179374.XA patent/CN117159594A/zh active Pending
- 2020-02-27 CN CN202311179517.7A patent/CN117159595A/zh active Pending
-
2021
- 2021-03-01 US US17/904,953 patent/US20230118958A1/en active Pending
- 2021-03-01 WO PCT/CN2021/078437 patent/WO2021170138A1/zh unknown
- 2021-03-01 JP JP2022576574A patent/JP2023516101A/ja active Pending
- 2021-03-01 CA CA3173276A patent/CA3173276A1/en active Pending
- 2021-03-01 KR KR1020227029973A patent/KR20220133282A/ko active Search and Examination
- 2021-03-01 AU AU2021226553A patent/AU2021226553A1/en active Pending
- 2021-03-01 EP EP21760816.5A patent/EP4112065A4/en active Pending
Patent Citations (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1223865A (zh) | 1998-01-20 | 1999-07-28 | 上海信谊药业有限公司 | 双歧三联活菌制剂及制备方法 |
US6368591B2 (en) | 1998-05-15 | 2002-04-09 | Shanghai Sine Pharmaceutical Corporation Ltd. | Beneficial microbe composition, new protective materials for the microbes, method to prepare the same and uses thereof |
CN101244090A (zh) | 2007-02-16 | 2008-08-20 | 信谊药厂 | 长型双岐杆菌培养基、制剂及其工艺 |
CN101244089A (zh) | 2007-02-16 | 2008-08-20 | 信谊药厂 | 嗜酸乳杆菌/粪肠球菌培养基、制剂及其工艺 |
CN103131647A (zh) | 2011-11-29 | 2013-06-05 | 上海信谊药厂有限公司 | 婴儿双岐杆菌及其制剂 |
CN103830278A (zh) | 2012-11-21 | 2014-06-04 | 上海信谊药厂有限公司 | 活菌冻干粉以及三联活菌制剂的制备方法 |
CN107847530A (zh) * | 2015-06-01 | 2018-03-27 | 芝加哥大学 | 通过控制共生微生物丛来治疗癌症 |
CN106110322A (zh) * | 2016-07-29 | 2016-11-16 | 安徽瀚海博兴生物技术有限公司 | 一种药物组合物及其在制备治疗癌症药物中的应用 |
WO2018226690A1 (en) * | 2017-06-05 | 2018-12-13 | The University Of Chicago | Microbiome biomarkers of immunotherapy responsiveness: diagnostic, prognostic and therapeutic uses thereof |
CN110063970A (zh) * | 2019-04-30 | 2019-07-30 | 上海心脉途医疗科技有限公司 | 与irAE相关的肠道菌群及irAE的治疗和预防方法 |
CN111096982A (zh) * | 2020-02-27 | 2020-05-05 | 上海上药信谊药厂有限公司 | 抗肿瘤组合物 |
Non-Patent Citations (2)
Title |
---|
MA WEIDONG, XU LIN,JIANG FENG: "Research progress of Gut microbiota in regulating the therapeutic effect of cancer", CHINESE JOURNAL OF SURGICAL ONCOLOGY, vol. 11, no. 3, 1 June 2019 (2019-06-01), pages 217 - 220, XP055841833, ISSN: 1674-4136, DOI: 10.3969 /j.issn.1674-4136.2019.03.016 * |
See also references of EP4112065A4 |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2023116283A1 (zh) * | 2021-12-22 | 2023-06-29 | 苏州普瑞森生物科技有限公司 | 一种抗结直肠肿瘤的乳酸肠球菌及其应用 |
CN114432458A (zh) * | 2022-01-21 | 2022-05-06 | 同济大学 | 一种细菌载药***及其制备方法 |
Also Published As
Publication number | Publication date |
---|---|
US20230118958A1 (en) | 2023-04-20 |
CN117159595A (zh) | 2023-12-05 |
CA3173276A1 (en) | 2021-09-02 |
JP2023516101A (ja) | 2023-04-17 |
AU2021226553A1 (en) | 2022-09-22 |
CN111096982A (zh) | 2020-05-05 |
CN117159594A (zh) | 2023-12-05 |
EP4112065A1 (en) | 2023-01-04 |
CN111096982B (zh) | 2023-09-12 |
KR20220133282A (ko) | 2022-10-04 |
EP4112065A4 (en) | 2024-04-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2021170138A1 (zh) | 抗肿瘤组合物 | |
WO2021170137A1 (zh) | 抗肿瘤组合物 | |
US20200384040A1 (en) | Use of bacteroides fragilis in preparation of medicament for treating and preventing tumor | |
US20170266239A1 (en) | Compositions for the Restoration of a Fecal Microbiota and Methods for Making and Using Them | |
CN111110852A (zh) | 抗肿瘤组合物 | |
Rommasi | Bacterial-based methods for cancer treatment: What we know and where we are | |
US20220000949A1 (en) | Antitumor effect potentiator | |
CN109771445B (zh) | 酪酸梭菌在制备诱导抗肿瘤免疫及免疫检查点抑制剂增敏制剂中的应用 | |
Diwan et al. | Microbial cancer therapeutics: A promising approach | |
JP2024098008A (ja) | 免疫チェックポイント阻害療法を促進するための組成物 | |
US20200197513A1 (en) | Nutraceutical blends | |
JP2024050573A (ja) | 腫瘍浸潤リンパ球(tils)を活性化する方法 | |
WO2015160314A1 (en) | Nutraceutical blend for the enhancement of the immune system | |
US20230106313A1 (en) | A bacterial composition for the treatment of cancer | |
CN113453697B (zh) | 用于根除幽门螺旋杆菌感染的新颖的益生菌 | |
US20170246223A1 (en) | Combination Therapy for Solid Tumour Cancer | |
Mishra et al. | Probiotics as Next Generation Strategy for Cancer Therapy | |
WO2023063918A1 (en) | Development and production of anticancer peptides of bacteriocin origin as biological and immunotherapeutic agents in cancer immunotherapy and as peptide antibiotics in infection immunotherapy | |
WO2024047527A1 (en) | Methods and compositions for preventing and treating chemotherapy-induced peripheral neuropathy | |
Sklyarova et al. | Рrospects for the methods of healing of the wound using bacteria |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 21760816 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 2022576574 Country of ref document: JP Kind code of ref document: A |
|
ENP | Entry into the national phase |
Ref document number: 3173276 Country of ref document: CA |
|
ENP | Entry into the national phase |
Ref document number: 20227029973 Country of ref document: KR Kind code of ref document: A |
|
ENP | Entry into the national phase |
Ref document number: 2021226553 Country of ref document: AU Date of ref document: 20210301 Kind code of ref document: A |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
ENP | Entry into the national phase |
Ref document number: 2021760816 Country of ref document: EP Effective date: 20220927 |